Influenza pandemics occur at irregular intervals and each has different characteristics in terms of severity and population groups most affected. One constant is that younger individuals are disproportionately infected;even in the great 1918 pandemic, there is evidence of relative sparing of those 65 years of age and older. Much of the community-based transmission in pandemic as well as seasonal influenza takes place in younger individuals, in part because of their susceptibility but also because of their social interaction patterns. During the last decade, in planning for an influenza pandemic, community mitigation strategies were developed which recommended various measures to produce social distancing. Many of the layered interventions involved restriction of individual activity and/or sequestration of cases. In the 2009 pandemic, such measures were never formally recommended, in part because of early difficulty in assessing severity. School closures were carried out for varying time periods, but many in reaction to local events rather than early as had been the planned approach. Thus, there are some, but not enough data on the effects of social distancing to make recommendations for future pandemics or even outbreaks of seasonal influenza. Universities are a place where transmission of influenza is facilitated because of the age of the individuals involved, their close contact with each other, and low vaccination coverage. We propose to study the effect of varying isolation periods on influenza transmission in University housing. Specifically, we will randomize large University residence halls (dormitories) to three sequestration protocols, which will be put into effect during periods of known influenza transmission. Those who develop influenza-like illnesses in randomized residence halls will a) not be asked to change their behaviors b) agree to remain in their rooms for 3 days c) agree to remain in their rooms for 6 days. Specimens will be collected for virus identification when the illness is first reported, as well as on day 3 and on day 6 from illness onset. The specimens will be run for type A and B influenza and other respiratory pathogens using CDC recommended probes and primers. Results will be analyzed to allow quantification of shedding patterns and statistical comparisons for influenza illness cases and respiratory illness cases will be examined between randomized residence halls. The hypothesis to be tested is that sequestration of individuals will reduce transmission within the residence hall via monitoring of residence halls through our study and visits to University Health Services. Voluntary isolation has been identified as one of the most efficient ways to reduce influenza transmission. The results, if positive, will confirm the acceptability and magnitude of effect that can be expected from such an intervention. It will also help in determining the number of days that such an exclusion should be practiced. The environment of a university dormitory, where variables can easily be identified and closely studied, will provide strong confidence in the generalizability of the findings. ! ! ! PUBLIC HEALTH RELEVANCE: The proposed study will assess the impact of varying isolation periods on risk of influenza in residence halls on the campus of University of Michigan. The findings from this study will have important public health implications, including identification of critical periods of illness transmission that may account for outbreaks in the school setting. The results of these studies may be used for setting specific national mitigation strategies where social distancing is a major component.